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1.
Int J Mol Sci ; 24(8)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37108090

RESUMO

Immunoglobulin gamma-3 chain C (IGHG3) levels have been detected in the blood and tissue of patients with systemic lupus erythematosus (SLE). This study aims to assess its clinical value by measuring and comparing levels of IGHG3 in different body fluids in patients with SLE. The levels of IGHG3 in saliva, serum, and urine from 181 patients with SLE and 99 healthy controls were measured and analyzed. In patients with SLE and healthy controls, salivary IGHG3 levels were 3078.9 ± 2473.8 and 1413.6 ± 1075.3 ng/mL, serum IGHG3 levels were 478.1 ± 160.9 and 364.4 ± 97.9 µg/mL, and urine IGHG3 levels were 64.0 ± 74.5 and 27.1 ± 16.2 ng/mL, respectively (all p < 0.001). Salivary IGHG3 was correlated with ESR (correlation coefficient [r], 0.173; p = 0.024). Serum IGHG3 was correlated with leukocyte count (r, -0.219; p = 0.003), lymphocyte count (r, 0.22; p = 0.03), anti-dsDNA antibody positivity (r, 0.22; p = 0.003), and C3 levels (r, -0.23; p = 0.002). Urinary IGHG3 was correlated with hemoglobin level (r, -0.183; p = 0.021), ESR (r, 0.204; p = 0.01), anti-dsDNA antibody positivity (r, 0.262; p = 0.001), C3 levels (r, -0.202; p = 0.011), and SLE disease activity index (r, 0.332; p = 0.01). Urinary IGHG3 was higher in patients with nephritis than in those without (119.5 ± 110.0 vs. 49.8 ± 54.4 ng/mL; p < 0.01). IGHG3 was increased in the saliva, serum, and urine of patients with SLE. While salivary IGHG3 was not identified to be specific to SLE disease activity, serum IGHG3 showed correlations with clinical characteristics. Urinary IGHG3 levels were associated with disease activity and renal involvement in SLE.


Assuntos
Líquidos Corporais , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Nefrite , Humanos , Saliva , Nefrite/complicações , Imunoglobulinas , Nefrite Lúpica/urina , Biomarcadores
2.
Macromol Rapid Commun ; 42(17): e2100305, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34347333

RESUMO

Tandem solar cells which are electrically connected with various photoactive materials have the potential to solve the current challenges by exceeding the theoretically limited efficiency of single junction solar cells. Here the first monolithic organic/silicon tandem cell is reported based on a semitransparent polymer on a crystalline silicon (c-Si) substrate. Herein, experimental results are presented for four-terminal (4-T) and monolithic two-terminal (2-T) organic/c-Si tandem cells using organic cells with an inverted n-i-p structure and c-Si cells with an n-type TOPCon structure with detailed analysis. The best 4-T tandem cell efficiency is 15.22%, and 2-T results show that the top (organic) and bottom (c-Si) cells are electrically connected by an open-circuit voltage over 1.4 V. Further, a simulated efficiency of over 20% using the organic/c-Si tandem is achieved, implying the tandem efficiency can be enhanced through further improvement of electric and optical characteristics with the optimization.


Assuntos
Energia Solar , Eletrodos , Polímeros , Silício , Luz Solar
3.
BMC Vet Res ; 14(1): 371, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30486820

RESUMO

BACKGROUND: Foot-and-mouth disease (FMD) can be controlled by either stamping out or vaccination, a choice which depends on both the economic importance of the livestock sector as well as the disease status. In FMD-free countries with vaccination, such as Korea, vaccination programs should guarantee prevention against transmission of FMD. Monitoring of vaccination programs is also essential for ensuring sufficient coverage that will limit the transmission of FMDV. There are several methods to screen FMD virus (FMDV) structural protein (SP) antibodies including SPCE (Solid-phase competitive ELISA), LPBE (Liquid-phase blocking ELISA), and VNT (Virus neutralization test). Among these, SPCE is widely used for serological monitoring since VNT-the gold standard method-has certain practical limitations, such as high costs in terms of time and labor. However, whether SPCE can ensure the vaccination status of individual animals and whole farms is unclear. In this study, SPCE, LPBE and VNT were compared with respect to correlation with each other and sensitivity at commercial pig farms. RESULTS: The positive results obtained by PrioCHECK SPCE differed from those obtained by LPBE and VNT. The sensitivity of SPCE relative to those of the other tests was fairly low. The raw data of SPCE were most highly correlated with those of VNT with XJ strain, while their positivity and negativity were most highly correlated with LPBE. The results of ROC analysis proposed new cut-off for PrioCHECK SPCE higher than the previous 50% inhibition. CONCLUSIONS: The high false positive rate of PrioCHECK SPCE suggested that high seropositivity by SPCE may not guarantee a true vaccination coverage. Adjusting the cut-off percentage (%) inhibition value for SPCE is needed to address this problem, and it is highly recommended that routine FMDV serological monitoring programs using PrioCHECK SPCE should be combined with alternative methods such as LPBE or VNT.


Assuntos
Anticorpos Antivirais/sangue , Febre Aftosa/prevenção & controle , Monitorização Imunológica/métodos , Testes Sorológicos/veterinária , Vacinação/veterinária , Animais , Ensaio de Imunoadsorção Enzimática/veterinária , Febre Aftosa/sangue , Vírus da Febre Aftosa/imunologia , Testes de Neutralização/veterinária , República da Coreia , Proteínas Estruturais Virais/imunologia , Vacinas Virais/normas
4.
BMC Infect Dis ; 16(1): 425, 2016 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-27538397

RESUMO

BACKGROUND: Enterovirus (EV) 71 is the main pathogen associated with hand, foot and mouth disease (HFMD) or herpangina. Outbreaks of HFMD caused by EV71 infection are associated severe neurological disease and high mortality rates in children. Several sporadic cases of EV71 infection occurred in the Republic of Korea (ROK) in 2000, and EV71 infections were not reported thereafter until 2006. In this prospective study, we report the epidemic and virologic characteristics of the EV71 endemic from 2007 to 2012 in the Republic of Korea. METHODS: We analyzed characteristics of the EV71 infection-associated epidemic from collected specimens and clinical information from 9987 patients with suspected EV infection from the National EV Surveillance System in ROK. To identify the EV71 subgenotype, the homology of viral protein 1 sequences obtained using reverse transcription polymerase chain reaction was compared with the sequences on other countries available from GenBank database. RESULTS: EV71 was detected in 585 (16.7 %) specimens (cerebrospinal fluid, stool or rectal swabs, throat swabs and blood) during study period and was most frequently observed during epidemic seasons in 2009-2012. Major manifestations due to EV71 infection were HFMD (62.2 %) and HFMD with severe neurological complications (28.4 %). Five deaths (0.9 %) due to EV71 infection occurred, with an increased mortality rate during the period after 2009. Most patients (476; 81.4 %) were less than 5 years of age. Analysis of the monthly distribution showed that there was an obvious seasonal pattern to the epidemics, with infections appearing from June to August. The major subgenotype of EV71 isolates circulating in ROK was the C4a strain, which has also appeared in China, Japan and Vietnam. CONCLUSIONS: This surveillance provided valuable data on the epidemic characteristics of EV71 infections in ROK during a 6-year period. Our findings provide data to assist during future outbreaks of EV71 and associated acute neurologic disease.


Assuntos
Enterovirus Humano A/genética , Doença de Mão, Pé e Boca/epidemiologia , Adolescente , Adulto , Líquido Cefalorraquidiano/virologia , Criança , Pré-Escolar , Estudos Transversais , Surtos de Doenças , Enterovirus Humano A/classificação , Enterovirus Humano A/isolamento & purificação , Fezes/virologia , Feminino , Genótipo , Doença de Mão, Pé e Boca/mortalidade , Doença de Mão, Pé e Boca/virologia , Humanos , Lactente , Masculino , Filogenia , RNA Viral/isolamento & purificação , RNA Viral/metabolismo , República da Coreia/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Proteínas Virais/genética , Proteínas Virais/metabolismo , Adulto Jovem
5.
Sensors (Basel) ; 16(1)2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26751453

RESUMO

We propose a solution-processable ultraviolet (UV) photodetector with a pn-heterojunction hybrid photoactive layer (HPL) that is composed of poly-n-vinylcarbazole (PVK) as a p-type polymer and ZnO nanoparticles (NPs) as an n-type metal oxide. To observe the effective photo-inducing ability of the UV photodetector, we analyzed the optical and electrical properties of HPL which is controlled by the doping concentration of n-type ZnO NPs in PVK matrix. Additionally, we confirmed that the optical properties of HPL dominantly depend on the ZnO NPs from the UV-vis absorption and the photoluminescence (PL) spectral measurements. This HPL can induce efficient charge transfer in the localized narrow pn-heterojunction domain and increases the photocurrent gain. It is essential that proper doping concentration of n-type ZnO NPs in polymer matrix is obtained to improve the performance of the UV photodetector. When the ZnO NPs are doped with the optimized concentration of 3.4 wt.%, the electrical properties of the photocurrent are significantly increased. The ratio of the photocurrent was approximately 10³ higher than that of the dark current.


Assuntos
Nanopartículas Metálicas/química , Nanocompostos/química , Polivinil/química , Óxido de Zinco/química , Processos Fotoquímicos , Espectrofotometria Ultravioleta
6.
Front Immunol ; 13: 886209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529863

RESUMO

Objectives: This study aimed to elucidate the potential of serum, urine, and saliva S100 calcium-binding protein A8 protein (S100A8) levels as biomarkers for systemic lupus erythematosus (SLE). Methods: Serum, urine, and saliva samples were obtained from 249 patients with SLE from the Ajou lupus cohort and 52 age- and sex-matched healthy controls (HCs). The concentrations of S100A8 were quantified using an ELISA, and a receiver operating characteristic curve was used to analyze whether they may be used as biomarkers for diagnosing SLE. Results: Among 249 SLE patients included in our study, the mean SLE disease activity index (SLEDAI)-2K was 7.16 ± 5.61, and the number of patients with lupus flare was 11. Patients with SLE showed a 2.7-fold increase in serum S100A8 levels compared with that in HCs (1,890.6 vs. 709 pg/ml, p < 0.001). In urine and saliva, the average S100A8 levels were significantly higher in patients with SLE compared with those in HCs (urine, 2,029.4 vs. 1,096.7 pg/ml, p = 0.001; saliva, 290,496.3 vs. 47,742 pg/ml, p < 0.001). For SLE diagnosis, the area under the receiver operating characteristic curve was 0.831 for serum S100A8 (95% CI, 0.765-0.897), 0.751 for urine S100A8 (95% CI, 0.648-0.854), and 0.729 for salivary S100A8 (95% CI, 0.646-0.812). Pearson's correlation analysis showed that S100A8 in serum, urine, and saliva was significantly associated with the SLEDAI (r = 0.267, p < 0.001; r = 0.274, p < 0.001; and r = 0.629, p < 0.001, respectively). Among the clinical manifestations, nephritis was the most influential factor related to SLE in the concentration of S100A8 in serum, urine, and saliva. Conclusion: This is the first study to show that the expression of S100A8 in serum, urine, and saliva is significantly higher in patients with SLE than in HCs and is associated with disease activity markers. Therefore, we suggest that S100A8 protein could be a potential biomarker for SLE.


Assuntos
Calgranulina A , Lúpus Eritematoso Sistêmico , Biomarcadores , Humanos , Saliva , Exacerbação dos Sintomas
7.
ACS Appl Bio Mater ; 5(8): 3816-3825, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35816421

RESUMO

The specific topography of biomaterials plays an important role in their biological interactions with cells and thus the safety of medical implants. Antifouling materials can be engineered with topographic features to repel microbes. Meanwhile, undesired topographies of implants can cause complications such as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). While the cause of BIA-ALCL is not well understood, it is speculated that textured surfaces are prone to bacterial biofilm formation as a contributing factor. To guide the design of safer biomaterials and implants, quantitative screening approaches are needed to assess bacterial adhesion to different topographic surface features. Here we report the development of a high-throughput microplate biofilm assay for such screening. The assay was used to test a library of polydimethylsiloxane (PDMS) textures composed of varying sizes of recessive features and distances between features including those in the range of breast implant textures. Outliers of patterns prone to bacterial adhesion were further studied using real-time confocal fluorescence microscopy. The results from these analyses revealed that surface area itself is a poor predictor for adhesion, while the size and spacing of topographic features play an important role. This high-throughput biofilm assay can be applied to studying bacteria-material interactions and rational development of materials that inhibit bacterial colonization.


Assuntos
Implantes de Mama , Linfoma Anaplásico de Células Grandes , Bactérias , Materiais Biocompatíveis , Biofilmes , Implantes de Mama/efeitos adversos , Humanos , Linfoma Anaplásico de Células Grandes/etiologia
8.
Biomaterials ; 268: 120595, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33360301

RESUMO

Microbes have remarkable capabilities to attach to the surface of implanted medical devices and form biofilms that adversely impact device function and increase the risk of multidrug-resistant infections. The physicochemical properties of biomaterials have long been known to play an important role in biofilm formation. More recently, a series of discoveries in the natural world have stimulated great interest in the use of 3D surface topography to engineer antifouling materials that resist bacterial colonization. There is also increasing evidence that some medical device surface topographies, such as those designed for tissue integration, may unintentionally promote microbial attachment. Despite a number of reviews on surface topography and biofilm control, there is a missing link between how bacteria sense and respond to 3D surface topographies and the rational design of antifouling materials. Motivated by this gap, we present a review of how bacteria interact with surface topographies, and what can be learned from current laboratory studies of microbial adhesion and biofilm formation on specific topographic features and medical devices. We also address specific biocompatibility considerations and discuss how to improve the assessment of the anti-biofilm performance of topographic surfaces. We conclude that 3D surface topography, whether intended or unintended, is an important consideration in the rational design of safe medical devices. Future research on next-generation smart antifouling materials could benefit from a greater focus on translation to real-world applications.


Assuntos
Aderência Bacteriana , Biofilmes , Bactérias , Materiais Biocompatíveis , Próteses e Implantes , Propriedades de Superfície
9.
Biofabrication ; 13(3)2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34102612

RESUMO

Green manufacturing has emerged across industries, propelled by a growing awareness of the negative environmental and health impacts associated with traditional practices. In the biomaterials industry, electrospinning is a ubiquitous fabrication method for producing nano- to micro-scale fibrous meshes that resemble native tissues, but this process traditionally utilizes solvents that are environmentally hazardous and pose a significant barrier to industrial scale-up and clinical translation. Applying sustainability principles to biomaterial production, we have developed a 'green electrospinning' process by systematically testing biologically benign solvents (U.S. Food and Drug Administration Q3C Class 3), and have identified acetic acid as a green solvent that exhibits low ecological impact (global warming potential (GWP) = 1.40 CO2eq. kg/L) and supports a stable electrospinning jet under routine fabrication conditions. By tuning electrospinning parameters, such as needle-plate distance and flow rate, we updated the fabrication of widely utilized biomedical polymers (e.g. poly-α-hydroxyesters, collagen), polymer blends, polymer-ceramic composites, and growth factor delivery systems. Resulting 'green' fibers and composites are comparable to traditional meshes in terms of composition, chemistry, architecture, mechanical properties, and biocompatibility. Interestingly, material properties of green synthetic fibers are more biomimetic than those of traditionally electrospun fibers, doubling in ductility (91.86 ± 35.65 vs. 45 ± 15.07%,n= 10,p< 0.05) without compromising yield strength (1.32 ± 0.26 vs. 1.38 ± 0.32 MPa) or ultimate tensile strength (2.49 ± 0.55 vs. 2.36 ± 0.45 MPa). Most importantly, green electrospinning proves advantageous for biofabrication, rendering a greater protection of growth factors during fiber formation (72.30 ± 1.94 vs. 62.87 ± 2.49% alpha helical content,n= 3,p< 0.05) and recapitulating native ECM mechanics in the fabrication of biopolymer-based meshes (16.57 ± 3.92% ductility, 33.38 ± 30.26 MPa elastic modulus, 1.30 ± 0.19 MPa yield strength, and 2.13 ± 0.36 MPa ultimate tensile strength,n= 10). The eco-conscious approach demonstrated here represents a paradigm shift in biofabrication, and will accelerate the translation of scalable biomaterials and biomimetic scaffolds for tissue engineering and regenerative medicine.


Assuntos
Bioimpressão , Materiais Biocompatíveis , Módulo de Elasticidade , Polímeros , Resistência à Tração , Engenharia Tecidual , Alicerces Teciduais
10.
Viruses ; 13(10)2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34696347

RESUMO

Equine parvovirus-hepatitis (EqPV-H) is a newly identified etiologic agent of Theiler's disease (TD). We present a case of EqPV-H-related fulminant hepatitis in a 14-year-old thoroughbred mare in Korea. The mare had acute hepatopathy and gastrointestinal symptoms, with abnormal liver-related blood parameters. The horse was born in the USA and imported to Korea in 2017, with no history of administration of equine biological products after entry into Korea. The horse was diagnosed with EqPV-H-associated hepatitis after abdominal ultrasonography, laparotomy, and nested polymerase chain reaction (PCR) and in situ hybridization (ISH) assays. The serum, nasal swab, oral swab, and liver biopsy were positive for EqPV-H according to the PCR assay. Genetic analysis of the partial NS1 gene of EqPV-H showed a unique nucleotide substitution, distinct from that in previously deposited strains. EqPV-H DNA was found not only in hepatocytes but also in bile duct epithelium and Kupffer cells, particularly via ISH. To the best of our knowledge, this is the first case of EqPV-H-associated TD in Asia, providing the first clinical evidence for viral shedding from the mouth and nose, and identification of EqPV-H in the liver. This study contributes to a better understanding of the pathological features of EqPV-H-associated TD.


Assuntos
Infecções por Enterovirus/virologia , Hepatite Viral Animal/virologia , Doenças dos Cavalos/virologia , Infecções por Parvoviridae/veterinária , Infecções por Parvoviridae/virologia , Parvovirinae , Parvovirus , Animais , Ásia , Feminino , Hepatócitos/patologia , Cavalos , Fígado/patologia , Parvovirinae/classificação , Filogenia , Reação em Cadeia da Polimerase , República da Coreia , Eliminação de Partículas Virais
11.
Anal Chem ; 82(18): 7828-34, 2010 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-20718428

RESUMO

The construction of a trypsin column for rapid and efficient protein digestion in proteomics is described. Electrospun and alcohol-dispersed polymer nanofibers were used for the fabrication of highly stable trypsin coatings, which were prepared by a two-step process of covalent attachment and enzyme cross-linking. In a comparative study with the trypsin coatings on as-spun and nondispersed nanofibers, it has been observed that a simple step of alcohol dispersion improved not only the enzyme loading but also the performance of protein digestion. In-column digestion of enolase was successfully performed in less than 20 min. By applying the alcohol dispersion of polymer nanofibers, the bypass of samples was reduced by filling up the column with well-dispersed nanofibers, and subsequently, interactions between the protein and the trypsin coatings were improved, yielding more complete and reproducible digestions. Regardless of alcohol dispersion or not, trypsin coatings showed better digestion performance and improved performance stability under recycled uses than covalently attached trypsin, in-solution digestion, and commercial trypsin beads. The combination of highly stable trypsin coatings and alcohol dispersion of polymer nanofibers has opened up a new potential to develop a trypsin column for online and automated protein digestion.


Assuntos
Álcoois/química , Eletricidade , Nanofibras/química , Polímeros/química , Proteínas/metabolismo , Tripsina/química , Tripsina/metabolismo , Sequência de Aminoácidos , Biocatálise , Cromatografia Líquida , Etanol/química , Modelos Moleculares , Conformação Molecular , Dados de Sequência Molecular , Fosfopiruvato Hidratase/análise , Fosfopiruvato Hidratase/química , Fosfopiruvato Hidratase/metabolismo , Proteínas/análise , Proteínas/química , Proteômica , Espectrometria de Massas em Tandem , Temperatura
12.
Biotechnol Bioeng ; 107(6): 917-23, 2010 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-20683853

RESUMO

An efficient protein digestion in proteomic analysis requires the stabilization of proteases such as trypsin. In the present work, trypsin was stabilized in the form of enzyme coating on electrospun polymer nanofibers (EC-TR), which crosslinks additional trypsin molecules onto covalently attached trypsin (CA-TR). EC-TR showed better stability than CA-TR in rigorous conditions, such as at high temperatures of 40 and 50°C, in the presence of organic co-solvents, and at various pH's. For example, the half-lives of CA-TR and EC-TR were 1.42 and 231 h at 40°C, respectively. The improved stability of EC-TR can be explained by covalent linkages on the surface of trypsin molecules, which effectively inhibits the denaturation, autolysis, and leaching of trypsin. The protein digestion was performed at 40°C by using both CA-TR and EC-TR in digesting a model protein, enolase. EC-TR showed better performance and stability than CA-TR by maintaining good performance of enolase digestion under recycled uses for a period of 1 week. In the same condition, CA-TR showed poor performance from the beginning and could not be used for digestion at all after a few usages. The enzyme coating approach is anticipated to be successfully employed not only for protein digestion in proteomic analysis but also for various other fields where the poor enzyme stability presently hampers the practical applications of enzymes.


Assuntos
Enzimas Imobilizadas/metabolismo , Nanofibras/química , Polímeros/química , Tripsina/metabolismo , Estabilidade Enzimática , Enzimas Imobilizadas/química , Meia-Vida , Ligação Proteica , Temperatura , Tripsina/química
13.
PLoS One ; 14(3): e0210477, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845175

RESUMO

Enterovirus (EV) 71 is the main pathogen associated with hand-foot-mouth disease (HFMD) and can lead to the disease with severe mortality in children. Since 2009, in the Republic of Korea, an outbreak of EV71 C4a infection with neurologic involvement emerged, where in HFMD involvement was identified and central nervous system complications were reported. In this study, EV71 C4a virus-like particles (VLPs) produced by recombinant technology were generated in a baculovirus expression system. To improve the production yield, EV71 VLP was constructed using the dual promoter system baculovirus P1 and 3CD (baculo-P1-3CD), which harbored both the structural protein-encoding P1 region under the control of the polyhedron promoter and the 3CD protease gene under the regulation of the CMV-IE, lef3, gp41, or chitinase promoters to augment the level of gene transcription. Efficient VLP expression was demonstrated through optimization of incubation time and insect cell type. In addition, to evaluate the potential of VLP as a vaccine candidate, we tested the neutralizing antibodies and total anti-EV71 IgG from the purified EV71 C4a VLP serum. The recombinant EV71 VLP exhibited the morphology of self-assembled VLP, as determined by electron microscopy. Use of baculo-P1-3CD-gp41 led to a high yield (11.3mg/L < 40kDa) of VLPs in High-FiveTM cells at 3 days post-infection. Furthermore, the potential of VLP as a vaccine was evaluated through the neutralizing ability elicited by the purified EV71 VLP after immunization of BALB/c mice, which was shown to induce potent and long-lasting humoral immune responses as evidenced by the cross-neutralization titer. Our results could be used to expedite the developmental process for vaccines under clinical trials and to ensure manufacturing consistency for licensing requirements.


Assuntos
Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/metabolismo , Enterovirus Humano A/genética , Vacinas de Partículas Semelhantes a Vírus/genética , Animais , Baculoviridae , Chlorocebus aethiops , Enterovirus Humano A/imunologia , Feminino , Engenharia Genética , Camundongos , Camundongos Endogâmicos BALB C , Células Sf9 , Vacinação , Vacinas de Partículas Semelhantes a Vírus/imunologia , Células Vero
14.
Vaccine ; 37(40): 5972-5978, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31455586

RESUMO

Infection with hepatitis E virus (HEV) has raised serious public health concerns worldwide. In this study, a nanogel-based vaccine encapsulating the capsid protein of rabbit HEV was developed and its protective efficacy was compared with a subunit vaccine. A total of 23 rabbits were divided into 5 groups: (1) negative control (n = 4), (2) positive control (n = 4), (3) nanogel control (n = 5), (4) nanogel vaccine (n = 5), and (5) subunit vaccine (n = 5). Rabbits were vaccinated two times, at weeks 0 and 1, with nanogel and subunit vaccines, respectively, and challenged with rabbit HEV at week 4. By week 11, rabbits vaccinated with the nanogel vaccine produced higher antibodies than those vaccinated with the subunit vaccine. Fecal viral shedding and viremia were identified in rabbits of the positive and nanogel control groups at weeks 6-10. However, there was no viral shedding and viremia in rabbits immunized with both the nanogel and subunit vaccines. Alanine aminotransferase and aspartate aminotransferase levels were not elevated in any rabbit. However, histopathological examination revealed much less hepatic inflammation in rabbits of the nanogel vaccine group compared to the positive and nanogel control groups. Significant increases in IL-12 and IFN-γlevels were identified from rabbits immunized with the nanogel vaccine. Collectively, these results indicate that the newly developed nanogel vaccine induced sufficient immunity leading to complete protection from HEV infection in rabbits. Application of this vaccine should be considered as a preventive measure against HEV infection in other animal species and humans.


Assuntos
Vírus da Hepatite E/imunologia , Hepatite E/imunologia , Nanogéis/administração & dosagem , Vacinas contra Hepatite Viral/imunologia , Animais , Anticorpos Antivirais/imunologia , Proteínas do Capsídeo/imunologia , Fezes/virologia , Imunização/métodos , Coelhos , Vacinação/métodos , Eliminação de Partículas Virais/imunologia
15.
Vaccine ; 36(24): 3445-3452, 2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29739716

RESUMO

Coxsackievirus belongs to the Enterovirus genus of the Picornaviridae family and is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD). Historically, outbreaks of HFMD have mainly been caused by enterovirus 71 and coxsackievirus A16. Recently, coxsackieviruses A6 and A10 have been associated with increased occurrences of sporadic HFMD cases and outbreak events globally. In this study, the immunogenicity of coxsackieviruses A6, A10, and A16 (CA6, CA10, and CA16), which were inactivated by formalin or ß-propiolactone (BPL) under different conditions, was evaluated as multivalent vaccine candidates. CA6 induced similar immune responses with both inactivation methods, and the immune efficacy of CA10 and CA16 was better following inactivation with BPL than with formalin. There was no sufficient cross-reactivity or cross-protectivity against heterologous strains in groups vaccinated with the BPL-inactivated (BI) monovalent vaccine. Sufficient neutralizing antibody and cell-mediated immune responses were induced in the BI-trivalent vaccinated group. These findings suggest that BI-CA6, CA10, and CA16 are potential multivalent vaccine candidates and that a multivalent vaccine is needed to control HFMD. The coxsackievirus multivalent vaccine could be useful for the development of effective HFMD vaccines.


Assuntos
Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Enterovirus Humano A/efeitos dos fármacos , Doença de Mão, Pé e Boca/prevenção & controle , Imunogenicidade da Vacina , Vacinas Virais/administração & dosagem , Animais , Proteção Cruzada , Enterovirus Humano A/imunologia , Enterovirus Humano A/patogenicidade , Feminino , Formaldeído/química , Doença de Mão, Pé e Boca/imunologia , Doença de Mão, Pé e Boca/mortalidade , Doença de Mão, Pé e Boca/virologia , Humanos , Imunidade Celular/efeitos dos fármacos , Interferon gama/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Propiolactona/química , Análise de Sobrevida , Potência de Vacina , Vacinas de Produtos Inativados , Vacinas de Subunidades Antigênicas , Vacinas Virais/imunologia
16.
PLoS One ; 13(10): e0202552, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30278051

RESUMO

Enterovirus 71 (EV71) is a major etiological agent of various public health issues, particularly in the Asia-Pacific region. EV71 causes hand-foot-and-mouth disease (HFMD) and is associated with serious neurological disorders in young children. A formalin-inactivated EV71 candidate vaccine (KCDC-HFMDV1-EV71) based on the C4 subgenotype was previously developed and confirmed to be a potential candidate vaccine for prevention of EV71 infection in mice. In this study, an inactivated EV71 vaccine was used for analysis of long-term immunogenicity and efficacy in cynomolgus monkeys, a common nonhuman primate model. The vaccine was immunized three times at 0, 4, and 8 weeks with either 20-µg doses of EV71 candidate vaccine formulated with aluminum hydroxide gel adjuvant or phosphate-buffered saline as a control. The group immunized with the inactivated EV71 showed significantly increased EV71-specific antibody and serum neutralizing antibody titers at 3 weeks after vaccination and maintained these elevated titers until the end of the experiment (54 weeks after vaccination). The sera from vaccinated cynomolgus monkeys showed a crossreactive neutralizing antibody response to the heterologous subtype of EV71 (B1-4, C1, and C2). These findings suggest that the inactivated EV71 candidate vaccine may be a potential vaccine candidate and valuable tool for the control of HFMD.


Assuntos
Enterovirus Humano A/imunologia , Infecções por Enterovirus/prevenção & controle , Doença de Mão, Pé e Boca/prevenção & controle , Vacinas de Produtos Inativados/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Enterovirus Humano A/patogenicidade , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/virologia , Doença de Mão, Pé e Boca/imunologia , Humanos , Macaca fascicularis/imunologia , Macaca fascicularis/virologia , Camundongos , Vacinação , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia
17.
J Exp Pharmacol ; 9: 81-91, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28814903

RESUMO

The aim of this study was to investigate the effects of Ixeris dentata (IXD) extract to improve the salivation rate in dry mouth induced by diabetes. Both control and diabetic rats were treated with a sublingual spray of either water or IXD extract to determine the effects of IXD on salivation. During the study, we observed that IXD extract treatment increased the salivary flow rate in diabetic rats. The expression of α-amylase was increased significantly in both saliva and glandular tissue lysates of IXD-treated diabetic rats. Aquaporin-5 protein expression was abnormally low in the salivary glands of diabetic rats, which increased hyposalivation and led to salivary dysfunction. However, a single oral spray of IXD extract drastically increased the expression of aquaporin-5 in salivary gland acinar and ductal cells in diabetic rats. Moreover, IXD extract induced expression of Na+/H+ exchangers in the salivary gland, which suggests that Na+/H+ exchangers modulate salivary secretions and aid in the fluid-secretion mechanism. Furthermore, transient treatment with IXD extract increased the intracellular calcium in human salivary gland cells. Taken together, these results suggest the potential value of an IXD extract for the treatment of diabetes-induced hyposalivation and xerostomia.

18.
PLoS One ; 12(5): e0178259, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28542556

RESUMO

Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD) frequently occurring in children. HFMD induced by EV71 can cause serious health problems and has been reported worldwide, particularly in the Asia-Pacific region. In this study, we assessed the immunogenicity of a formalin-inactivated HFMD vaccine using an EV71 strain (FI-EV71 C4a) isolated from a Korean patient. The vaccine candidate was evaluated in mice to determine the vaccination doses and vaccine schedules. BALB/c mice were intramuscularly administered 5, 10, or 20 µg FI-EV71 vaccine, followed by a booster 2 weeks later. EV71-specific antibodies and neutralizing antibodies were induced and maintained until the end of the experimental period in all vaccinated groups. To determine the effectiveness of adjuvant for the EV71 vaccine, three adjuvants, i.e., aluminium hydroxide gel, monophosphoryl lipid A, and polyinosinic-polycytidylic acid, were administered separately with the FI-EV71 vaccine to mice via the intramuscular route. Mice administered the FI-EV71 vaccine formulated with all three adjuvants induced a significantly increased antibody response compared with that of the single adjuvant groups. The vaccinated group with triple adjuvants exhibited more rapid induction of EV71-specific and neutralizing antibodies than the other groups. These results suggested that the role of adjuvant in inactivated vaccine was important for eliciting effective immune responses against EV71. In conclusion, our results showed that FI-EV71 was a potential candidate vaccine for prevention of EV71 infection.


Assuntos
Enterovirus Humano A/imunologia , Doença de Mão, Pé e Boca/imunologia , Doença de Mão, Pé e Boca/prevenção & controle , Vacinas Virais/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Relação Dose-Resposta Imunológica , Enterovirus Humano A/isolamento & purificação , Feminino , Doença de Mão, Pé e Boca/virologia , Humanos , Imunidade Celular , Esquemas de Imunização , Imunoglobulina G/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , República da Coreia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/farmacologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia
19.
J Neurosurg Spine ; 5(1): 83-5, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16850964

RESUMO

Atlantoaxial fixation in which C1-2 screw-rod fixation is performed is a relatively new method. Because reports about this technique are rather scant, little is known about its associated complications. In this report the authors introduce hypoglossal nerve palsy as a complication of this novel posterior atlantoaxial stabilization method. A 67-year-old man underwent a C1-2 screw-rod fixation for persistent neck pain resulting from a Type 2 odontoid fracture that involved disruption of the transverse atlantal ligament. Posterior instrumentation in which a C-1 lateral mass screw and C-2 pedicle screw were placed was performed. Postoperatively, the patient suffered dysphagia with deviation of the tongue to the left side. At the 4-month follow-up examination, bone fusion was noted on plain x-ray studies of the cervical spine. His hypoglossal nerve palsy resolved completely 2 months postoperatively. To the authors' knowledge, this is the first report in the literature of hypoglossal nerve palsy following C1-2 screw-rod fixation. The hypoglossal nerve is one of the structures that can be damaged during C-1 lateral mass screw placement.


Assuntos
Parafusos Ósseos/efeitos adversos , Fixação Interna de Fraturas/efeitos adversos , Doenças do Nervo Hipoglosso/etiologia , Processo Odontoide/lesões , Fraturas da Coluna Vertebral/cirurgia , Fusão Vertebral/efeitos adversos , Idoso , Fixação Interna de Fraturas/instrumentação , Humanos , Masculino , Fusão Vertebral/instrumentação
20.
J Clin Virol ; 85: 13-16, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27816018

RESUMO

BACKGROUND: Enterovirus 71 (EV71) is an important causative agent of hand-foot-and-mouth disease with severe neurological complications, which may lead to death in children. Large outbreaks caused by EV71 have frequently occurred in Asia-Pacific region. OBJECTIVES: In Korea, the outbreaks have been caused by EV71 subgenogroups C3, and C4. Only genogroup C, especially subgenogroup C1, C3, C4, and C5, has been detected by the national enterovirus surveillance system in Korea. This study reports the first isolation of EV71 A1451 strain, which belongs to subgenogroup C2. STUDY DESIGN: EV71 was isolated from a Korean patient with meningoencephalitis. Complete genome analysis and phylogenetic analysis was performed to identify the characteristics of the strain. RESULTS: Comparative genome analysis of the A1451 strain indicated that this novel C2 strain is associated with the Taiwan strains, which are recombinant virus combined with subgenogroup C2 and B3. CONCLUSIONS: Because the subgenogroup B3 was not previously detected in Korea, the A1451 strain is regarded as an imported recombinant virus. Periodic surveillance of EV71 is required to control the spread of this disease and its introduction from overseas.


Assuntos
Enterovirus Humano A/genética , Enterovirus Humano A/isolamento & purificação , Infecções por Enterovirus/virologia , Genótipo , Meningoencefalite/virologia , Ásia , Pré-Escolar , Análise por Conglomerados , Enterovirus Humano A/classificação , Genoma Viral , Humanos , Filogenia , República da Coreia , Análise de Sequência de DNA
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